What should I do if after finishing the induction sessions my patient is still not in clinical remission although they have experienced improvement?

Dr. Iago Rodríguez Lago

After the induction part the induction therapy with apheresis, we can face different scenarios. We can see patients that have had full response with biomarkers have normalized and they are also in clinical remission. But we can see also patients with partial response. This is similar to other medical therapies and we have here different options. We can retreat the patient with another induction therapy with apheresis and we know that these patients that have a response to one previous therapy with apheresis can respond to a second therapy. We can start the patient on maintenance therapy with apheresis and this means one to two apheresis per month and this is also beneficial. And we can also combine different medical therapies with apheresis, not only speaking about steroids or mesalazine that are the most frequent ones, but also with immunosuppressives or biological therapies. So, depending on the scenario that the patient is suffering on the natural and the previous history of the disease, we can see different options and we can decide on the future therapy of the patient.

References:

• Domènech, E., et al Use of granulocyte/monocytapheresis in ulcerative colitis: A practical review from a European perspective. World journal of gastroenterology, 2021; 27(10), 908–918.
• Fukuchi T, Kawashima K, Koga H, Utsunomiya R, Sugiyama K, Shimazu K, Eguchi T, Ishihara S. Induction of mucosal healing by intensive granulocyte/monocyte adsorptive apheresis (GMA) without use of corticosteroids in patients with ulcerative colitis: long-term remission maintenance after induction by GMA and efficacy of GMA re-treatment upon relapse. J Clin Biochem Nutr. 2022 Mar;70(2):197-204.

Dr. Eugeni Domènech

If a patient is still active after the schedule of induction apheresis regimen, there are several ways to follow with the patient and it will depend mainly on the degree of the disease activity. And in this sense, I think that if the patient remains with high activity of the disease, I think that the common sense shows that it is better to just change treatment. If the patient is mildly or moderately active, then we can follow several pathways. First, we can follow on GMA. We can, although intensified GMA, or we can add some other drug therapies to GMA for instance, biological therapies or whatever you want. It will also depend on if the patient is still on combination therapy with GMA or is in monotherapy. If the patient is on combination therapy, there are not so many solutions to this. If the patient is on monotherapy, we can add other therapies, as I said before, just combining GMA with biological.

References:

• Domènech, E., et al Use of granulocyte/monocytapheresis in ulcerative colitis: A practical review from a European perspective. World journal of gastroenterology, 2021 27(10), 908–918. 
• Cabriada, J.L., Rodríguez-Lago, I. Granulocitoaféresis en 2017. Puesta al día. Enfermedad Inflamatoria Intestinal 2017 (16) 2, 62-69.
• PRODIGGEST CLINICAL PRACTICE PROTOCOLS: Rational use of granulocytopheresis in inflammatory bowel disease 2019.
• Yoko Yokoyama, Koji Sawada, Nobuo Aoyama,  et al:  Efficacy of Granulocyte and Monocyte Adsorptive Apheresis in Patients With Inflammatory Bowel Disease Showing Lost Response to Infliximab, Journal of Crohn’s and Colitis 2020,1-10.

Dra. Pilar Nos

Partial responses to the treatment occur with all types of drug. In a complex situation, my patient hasn’t responded at all. Now what? So, in these cases we have options ranging from giving more accelerated regimens of two sessions per week through to optimising another treatment. If we don’t have the salicylates at maximum doses we can increase them, if we don’t have topical treatment that well optimized, we can increase it, we can increase the number of sessions. It always depends on the patient’s tolerance and the clinical situation. Of course, partial responses remain a problem today. This is where the option of combined therapies also comes into play. As it is such a safe drug, no not a drug a medical device, it can be combined with a different biological immunomodulator drug or JAK-inhibitor to wait for the synergistic effect.

References:

• Domènech, E., et al Use of granulocyte/monocytapheresis in ulcerative colitis: A practical review from a European perspective. World journal of gastroenterology, 2021; 27(10), 908–918.
• Fukuchi T, Kawashima K, Koga H, Utsunomiya R, Sugiyama K, Shimazu K, Eguchi T, Ishihara S. Induction of mucosal healing by intensive granulocyte/monocyte adsorptive apheresis (GMA) without use of corticosteroids in patients with ulcerative colitis: long-term remission maintenance after induction by GMA and efficacy of GMA re-treatment upon relapse. J Clin Biochem Nutr. 2022 Mar;70(2):197-204.

Dr. Francisco Fernández

If the patient has not achieved clinical remission after the induction process, if we consider that the treatment could be the best option for this patient, we can consider maintenance sessions. At our centre, we have a long experience in this sense and there have been patients who have had a response rather than a remission to the induction cycle but who, with maintenance sessions, sometimes fortnightly or monthly, have achieved a remission that otherwise would have required the use of immunosuppressants or biologics.

References:

• Domènech, E., et al Use of granulocyte/monocytapheresis in ulcerative colitis: A practical review from a European perspective. World journal of gastroenterology, 2021; 27(10), 908–918.
• Fukuchi T, Kawashima K, Koga H, Utsunomiya R, Sugiyama K, Shimazu K, Eguchi T, Ishihara S. Induction of mucosal healing by intensive granulocyte/monocyte adsorptive apheresis (GMA) without use of corticosteroids in patients with ulcerative colitis: long-term remission maintenance after induction by GMA and efficacy of GMA re-treatment upon relapse. J Clin Biochem Nutr. 2022 Mar;70(2):197-204.
• Naganuma M, Yokoyama Y, Motoya S, Watanabe K, et al.:CAPTAIN study Group. Efficacy of apheresis as maintenance therapy for patients with ulcerative colitis in an open-label prospective multicenter randomised controlled trial. J Gastroenterol. 2020 Apr;55(4):390-400.
• Sakuraba A, Sato T, Morohoshi Y, Matsuoka K, et al.:Intermittent granulocyte and monocyte apheresis versus mercaptopurine for maintaining remission of ulcerative colitis: a pilot study. Ther Apher Dial. 2012 Jun;16(3):213-8.

Dr. Daniel Ginard

We say that, if we have achieved a patient response after the induction but we don’t have complete remission, we can try maintenance therapy. Adding a few more sessions, giving a maintenance treatment, but above all it will depend on what line of treatment we are in, because sometimes we don’t have the same objectives in a patient in the first line of treatment, where we have other options, as we do in a patient where we are using it as a rescue treatment after several lines of treatment, with several different biologics, where sometimes the response is the maximum we can achieve with these patients or we have to be more patient until we achieve remission.

If there has been a response, a decrease in calprotectin, a clinical improvement, and after the induction we have not achieved a complete response, I would finish off with a few more sessions and add maintenance treatment.